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1.
Immunopharmacol Immunotoxicol ; 45(6): 719-729, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37581412

RESUMO

BACKGROUND: Due to the increase of the elderly's population and related social and economic problems, it is very important to provide strategies on health. In this regard, induction of T lymphocytes responses, the most important cells of the immune system, may be a good approach. Among different agents considered as antiaging factors, mTORC1 pathway inhibitors are significant. So, the purpose of this study was to evaluate the effect of two mTORC1 inhibitors, Everolimus and Metformin, on age-related features of activated T cells. MATERIALS AND METHODS: Optimum doses of drugs was determined with evaluating the effect of treatments on IL-2 gene expression. T cells isolated from old and young mice were treated with drugs and PHA. IL-2 production was evaluated by ELISA. Also, the expression of CD28, PD-1, and KLRG-1, proliferation, and intracellular oxidative stress were assessed by flow cytometry-based assays, phenotyping, CFSE, and DCF-DA assay respectively. RESULTS: Both drugs increased IL-2 production in the T cells of old mice. Also, using drugs especially Metformin could improve age-related phenotypical markers and increase the proliferation of T cells of old mice significantly. In addition, Metformin and Everolimus reduced intracellular oxidative stress in aged cells. However, the effect of both drugs on the T cells of young mice wasn't significant or was in opposite to the results of old mice T cells. DISCUSSION: In line with studies noting mTOR inhibitors as antiaging drugs, Metformin and Everolimus may improve T cells affected from aging in vitro, and a decrease in intracellular oxidative stress may be one of their mechanism of function.


Assuntos
Everolimo , Metformina , Humanos , Animais , Camundongos , Idoso , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Everolimo/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Interleucina-2 , Metformina/farmacologia , Linfócitos T/metabolismo , Envelhecimento
2.
J Acoust Soc Am ; 149(2): 1085, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33639823

RESUMO

A numerical technique is proposed for synthesizing realizations of airfoil surface pressure induced by incoming turbulence. In this approach, realization of the surface pressure field is expressed as a set of uncorrelated wall plane waves. The amplitude of these plane waves is determined from the power spectrum density function of the incoming upwash velocity fluctuation and the airfoil aeroacoustic transfer function. The auto-spectrum of the surface pressure is obtained from an ensemble average of different realizations. The numerical technique is computationally efficient as it rapidly converges using a relatively small number of realizations. The surface pressures for different airfoils excited by incoming turbulence are numerically predicted, and the results are compared with experimental data in the literature. Further, the unsteady force exerted on an airfoil due to the airfoil-turbulence interaction is also computed, and it is shown to be in very good agreement with analytical results.

3.
Acta Endocrinol (Buchar) ; 16(1): 68-73, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32685041

RESUMO

BACKGROUND: Although thyroid nodules are a common finding in the general population, determining the clinically important nodules is essential. We investigated thyroid nodules or cysts by thyroid ultrasonography (US) in patients with ß-thalassemia major (ß-TM) and intermedia (ß-TI). We also report a ß-TI patient who was diagnosed with thyroid cancer six months before our screening. METHODS: In this cross-sectional study, 178 patients with ß-thalassemias referred to the Thalassemia Clinic in a tertiary hospital affiliated to Shiraz University of Medical Sciences were investigated, from January to June 2016, by US. RESULTS: Thyroid nodules or cysts were detected in 11 patients [total: 6.17 %; 8 patients with ß-TM (8.2%) and 3 patients with ß-TI (3.7%)]. All nodules were < 1 cm in diameter and were not suspicious of malignancy. All patients, after 1 year of thyroid US follow-up, did not show any significant change in favor of malignancy. CONCLUSION: Based on our results, the frequency of thyroid nodules was similar to what was reported in the general population. However, a long-term follow-up of these patients is recommended because of the potential carcinogenic effects of iron and hepatitis C infection (HCV). To achieve more precise information, collaborative multicenter studies should be considered.

4.
Environ Res ; 170: 433-442, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30634139

RESUMO

Human exposure to persistent organic pollutants (POPs) begins during pregnancy and may cause adverse health effects in the fetus or later in life. The present study aimed to assess prenatal POPs exposure to Tanzanian infants and evaluate the distribution of POPs between breast milk, maternal blood, placenta and cord blood. For assessment of prenatal exposure, 48 maternal blood samples from Mount Meru Regional Referral Hospital (MMRRH), Arusha Tanzania, were analyzed for organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), brominated flame retardants (BFRs), dioxin-like (DL) activity and perfluorinated alkyl substances (PFASs). For evaluation of POPs distribution between maternal/infant compartments, breast milk, placenta and cord blood corresponding to the maternal blood were analyzed for OCPs, PCBs and BFRs. In maternal blood, p,p´- DDE was detected in 100% of the samples ranging between 29 and 1890 ng/g lipid weight (lw). PCB-153 was the only PCB detected in maternal blood, with detection rate of 29% and concentrations up to 116 ng/g lw. BDE-47 was detected in 65% of the maternal blood samples, ranging between

Assuntos
Poluentes Ambientais/metabolismo , Leite Humano/metabolismo , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Monitoramento Ambiental , Família , Feminino , Sangue Fetal , Humanos , Lactente , Quênia , Exposição Materna/estatística & dados numéricos , Placenta , Bifenilos Policlorados/metabolismo , Gravidez , Tanzânia/epidemiologia
5.
J Endocrinol Invest ; 42(12): 1467-1476, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31228105

RESUMO

PURPOSE: Transfusion-dependent beta-thalassemia (TDT) patients suffer from various endocrinopathies. The main contributing factor associated with these complications is iron overload, secondary to frequent blood transfusions. To improve patients' quality of life, we evaluated the prevalence of endocrine disorders while considering the associated factors for further assessment. METHODS: Seven hundred thirteen transfusion-dependent thalassemia patients with age range 10-62 years were enrolled in this study. Serum calcium, phosphorous, fast blood sugar, ferritin, 25-OH vitamin D, free thyroxin, thyroid-stimulating hormone and parathyroid hormone were assessed. Bone mineral density was measured by dual-energy X-ray absorptiometry. RESULTS: In total, 86.8% of the TDT patients suffered from at least one endocrinopathy. The prevalence of endocrinopathies in descending order of frequency was low bone mass (72.6%), hypogonadism (44.5%), diabetes mellitus (15.9%), hypoparathyroidism (13.2%), and hypothyroidism (10.7%). Age, body mass index and splenectomy were significantly associated with most of the endocrine disorders. CONCLUSION: Endocrine complications are frequently observed in TDT patients. Splenectomy is a major risk factor and should be generally avoided unless it is highly indicated. Periodic surveillance of endocrine function and proper management of iron overload are advised.


Assuntos
Doenças do Sistema Endócrino/epidemiologia , Qualidade de Vida , Talassemia/epidemiologia , Absorciometria de Fóton , Adolescente , Adulto , Densidade Óssea/fisiologia , Cálcio/sangue , Criança , Doenças do Sistema Endócrino/sangue , Feminino , Ferritinas/sangue , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fósforo/sangue , Prevalência , Fatores de Risco , Talassemia/sangue , Tireotropina/sangue , Tiroxina/sangue , Adulto Jovem
6.
J Endocrinol Invest ; 42(10): 1181-1189, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30963466

RESUMO

PURPOSE: NADPH oxidase 5 (NOX5), the main isoform of NOX in spermatozoa, has been recognized as the main active generators of reactive oxygen species (ROS), including superoxide anion (O 2 -. ) and hydrogen peroxide (H2O2). ROS have been shown to play important roles in many physiological and pathological conditions in spermatozoa. The present study aims to investigate the alterations of NOX5 protein expression and oxidative stress (OS) status in asthenozoospermic men compared to normozoospermic men. METHODS: Semen samples were collected from 25 asthenozoospermic men and 28 normozoospermic men. In this study, NOX5 protein expression was evaluated by Western blotting. An OS status was evaluated by measuring of ROS (O 2 -. and H2O2), DNA damage and plasma membrane integrity in spermatozoa. RESULTS: The protein expression of NOX5 (p < 0.0001) was remarkably higher in asthenozoospermic men in comparison to normozoospermic men. In addition, the percentages of intracellular O 2 -. (p < 0.0001), H2O2 (p < 0.0001) in viable spermatozoa, apoptotic sperm cells with altered plasma membrane (p < 0.001) and DNA damage (p = 0.001) were significantly increased in asthenozoospermic men compared to normozoospermic men. CONCLUSIONS: The present study provides evidence that the overexpression of NOX5 protein may induce excessive ROS production and oxidative stress damages to DNA and plasma membrane integrity in asthenozoospermic men.


Assuntos
Astenozoospermia/genética , Astenozoospermia/metabolismo , NADPH Oxidase 5/genética , Estresse Oxidativo/fisiologia , Espermatozoides/metabolismo , Adulto , Estudos de Casos e Controles , Membrana Celular/metabolismo , Dano ao DNA/genética , Fragmentação do DNA , Regulação Enzimológica da Expressão Gênica , Humanos , Infertilidade Masculina/genética , Infertilidade Masculina/metabolismo , Masculino , Espécies Reativas de Oxigênio/metabolismo , Sêmen/metabolismo , Análise do Sêmen
7.
J Chem Phys ; 149(1): 014702, 2018 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-29981550

RESUMO

A hydrogen atom can either physisorb or chemisorb onto a graphene surface. To describe the interaction of H with graphene, we trained the C-C, H-H, and C-H interactions of the ReaxFF CHO bond order potential to reproduce Density Functional Theory (DFT) generated values of graphene cohesive energy and lattice constant, H2 dissociation energy, H on graphene adsorption potentials, and H2 formation on graphene using the Eley-Rideal (ER) and Langmuir-Hinshelwood (LH) processes. The results, generated from the trained H-graphene potentials, are in close agreement with the corresponding results from DFT. The advantage of using optimized CH potentials is, for example, the inclusion of physisorption interactions and quantum mechanical features of chemical bonding in the functional forms of the potentials. The trained CH potentials are utilized to study the energetics of formation of an H2 molecule on graphene using the Eley-Rideal and Langmuir-Hinshelwood processes. Potential energy surfaces for the formation of H2 through ER are generated for the collinear and oblique approach of the second hydrogen atom. Energetics of the formation of H2 through LH is studied for a variety of cases such as when hydrogen atoms are chemisorbed or physisorbed and when hydrogen occupies ortho, meta, or para chemisorption sites. The likelihood of H2 formation through LH for various configurations is discussed. Furthermore, the tunneling probability of an atom through a continuous symmetric/asymmetric barrier is calculated and applied to an adsorbed hydrogen atom on graphene.

8.
Haemophilia ; 23(4): 575-582, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28440004

RESUMO

INTRODUCTION: A room temperature stable formulation of recombinant activated factor VII (NovoSeven® ), allowing convenient storage and therefore improved treatment access, has been developed. Bioequivalence to the previous NovoSeven® was demonstrated in healthy humans, leading to European approval (2008). Although no confirmed cases of neutralising antibodies to rFVIIa in patients with haemophilia A or B have been observed with the original formulation, changes in formulation or storage condition may alter immunogenicity. AIM: SMART-7™ was designed to investigate the safety of NovoSeven® in a real-world setting in patients with haemophilia A or B with inhibitors. METHODS: Study medication was not provided by the sponsor, and treatment was at the discretion of the treating physician, in accordance with the local label. Patient baseline information was collected at enrolment. Information on safety, drug exposure and bleeding episodes was collected and FVII antibody screening was encouraged at baseline and performed at the investigator's discretion. RESULTS: Fifty-one patients were enrolled and 31 completed the study. Forty-one adverse events (AEs) were reported in 23 patients; 25 AEs in 14 patients were serious. No thromboembolic events were observed. Although four cases of reduced therapeutic response were reported, FVII antibody screening was negative. Forty-eight patients experienced 618 bleeding episodes and 93.4% of 609 evaluated bleeds were stopped by treatment. Of the 538 bleeding episodes treated with NovoSeven® monotherapy, 94.2% stopped by end of treatment. CONCLUSION: Data collected during the SMART-7™ study revealed no treatment-related safety issues and no FVII-binding antibodies for patients treated with NovoSeven® under real-world conditions.


Assuntos
Fator VIIa/efeitos adversos , Fator VIIa/uso terapêutico , Hemofilia A/tratamento farmacológico , Hemofilia B/tratamento farmacológico , Segurança , Temperatura , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estabilidade de Medicamentos , Fator VIIa/farmacologia , Feminino , Hemofilia A/complicações , Hemofilia B/complicações , Hemorragia/complicações , Humanos , Lactente , Internacionalidade , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento , Adulto Jovem
9.
Eur J Clin Microbiol Infect Dis ; 36(11): 2259-2261, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28707065

RESUMO

Nasopharyngeal aspirate (NPA) Bordetella pertussis-specific IgA antibody assay using whole-cell (WC) antigen has previously been shown to have promise in the diagnosis of patients with suspected pertussis. Recently, the use of WC assays in serum have been replaced by pertussis toxin (PT) because of specificity concerns. In this study, PT and WC B. pertussis-specific IgA antibody was assayed in 491 NPAs. Specimens also had molecular testing for the presence of B. pertussis and B. parapertussis as per the usual laboratory protocol. Positive concordance of the two serological assays was 51.2%, negative concordance was 67.5% and total concordance was 75.8%. 99 of 119 discordant specimens were resolved by utilising the B. pertussis polymerase chain reaction (PCR) result and clinical status, and yielded a sensitivity of 57.6% and a specificity 97.7% for WC, with 90.2% and 93.1%, respectively, for the PT assay (p < 0.00025 and 0.025-0.01). In contrast, the sensitivity of PCR was only 19.1% in this cohort. We conclude that specificity is not a significant issue for mucosal pertussis-specific IgA assays using WC, but the superior sensitivity of the PT assay favours the latter method. This assay, combined with PCR assays, should significantly improve the diagnosis of pertussis cases.


Assuntos
Anticorpos Antibacterianos/imunologia , Bordetella parapertussis/isolamento & purificação , Bordetella pertussis/isolamento & purificação , Imunoglobulina A/imunologia , Toxina Pertussis/imunologia , Coqueluche/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/sangue , Austrália , Bordetella parapertussis/genética , Bordetella parapertussis/imunologia , Bordetella pertussis/genética , Bordetella pertussis/imunologia , Criança , Pré-Escolar , DNA Bacteriano/genética , Feminino , Humanos , Imunoglobulina A/sangue , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Mucosa/microbiologia , Nasofaringe/microbiologia , Reação em Cadeia da Polimerase/métodos , Estudos Prospectivos , Sensibilidade e Especificidade , Adulto Jovem
10.
Health Qual Life Outcomes ; 15(1): 105, 2017 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-28521836

RESUMO

BACKGROUND: The use of preference-elicitation tasks for valuing health states is well established, but little is known about whether these preferences are informed. Preferences may not be informed because individuals with little experience of ill health are asked to value health states. The use of uninformed preferences in cost-effectiveness can result in sub-optimal resource allocation. The aim of this study was to pilot a novel method to assess whether members of the public are informed about health states they value in preference-elicitation tasks. METHODS: The general public was said to be informed if the expectations of the public about the effect of ill health on people's lives were in agreement with the experience of patients. Sixty-two members of the public provided their expectations of the consequences of ill health on five life domains (activities, enjoyment, independence, relationships, and avoiding being a burden). A secondary dataset was used to measure patient experience on those five consequences. RESULTS: There were differences between the expectations of the public and the experience of patients. For example, for all five life consequences the public underestimated the effects of problems in usual activities compared to problems in mobility. They also underestimated the effect of 'anxiety or depression' compared to physical problems on enjoyment of life and on the quality of personal relationships. CONCLUSIONS: This proof-of-concept study showed that it is possible to test whether preferences are informed. This study should be replicated using a larger sample. The findings suggest that preferences over health states in this sample are not fully informed because the participants do not have accurate expectations about the consequences of ill health. These uninformed preferences may not be adequate for allocation of public resources, and research is needed into methods to make them better informed.


Assuntos
Atividades Cotidianas , Nível de Saúde , Qualidade de Vida , Adulto , Atitude Frente a Saúde , Análise Custo-Benefício , Depressão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor , Projetos Piloto , Vigilância da População , Autocuidado/psicologia
11.
Environ Res ; 154: 425-434, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28196346

RESUMO

This is the first study to report organochlorines (OCs), including chlorinated pesticides (OCPs) and polychlorinated biphenyls (PCBs) in human milk from Tanzania. The main aims of this study were to assess the level of contamination and the possible health risks related to OC exposure in nursing infants from the Northern parts of Tanzania. Ninety-five healthy mother-infant couples attending Mount Meru Regional Referral Hospital (MMRRH), Arusha, Tanzania, were assessed for associations between maternal/infant characteristics, i.e. mother's age, BMI, gestational weight gain, occupation, residence and fetal growth parameters and breast milk levels of OCPs, such as dichlorodiphenyltrichloroethane (DDT) and its metabolites, dieldrin and PCBs. p,p'-DDE and p,p'-DDT were detected in 100% and 75% of the breast milk samples, respectively, and ranged between 24 and 2400ng/g lipid weight (lw) and

Assuntos
DDT/análise , Diclorodifenil Dicloroetileno/análise , Exposição Ambiental/análise , Hidrocarbonetos Clorados/análise , Exposição Materna , Leite Humano/química , Praguicidas/análise , Adulto , Aleitamento Materno , Monitoramento Ambiental , Poluentes Ambientais/análise , Feminino , Humanos , Lactente , Saúde do Lactente , Quênia , Bifenilos Policlorados/análise , Gravidez , Medição de Risco , Tanzânia , Adulto Jovem
12.
Nano Lett ; 16(3): 1803-7, 2016 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-26859711

RESUMO

We report measurements of the shot noise on single-molecule Au-1,4-benzenedithiol-Au junctions, fabricated with the mechanically controllable break junction (MCBJ) technique at 4.2 K in a wide range of conductance values from 10(-2) to 0.24 conductance quanta. We introduce a simple measurement scheme using a current amplifier and a spectrum analyzer and that does not imply special requirements regarding the electrical leads. The experimental findings provide evidence that the current is carried by a single conduction channel throughout the whole conductance range. This observation suggests that the number of channels is limited by the Au-thiol bonds and that contributions due to direct tunneling from the Au to the π-system of the aromatic ring are negligible also for high conductance. The results are supported by quantum transport calculations using density functional theory.

13.
Haemophilia ; 22(5): 752-9, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27338009

RESUMO

INTRODUCTION: A paucity of data exists on the incidence, diagnosis and treatment of bleeding in women with inherited factor VII (FVII) deficiency. AIM: Here we report results of a comprehensive analysis from two international registries of patients with inherited FVII deficiency, depicting the clinical picture of this disorder in women and describing any gender-related differences. METHODS: A comprehensive analysis of two fully compatible, international registries of patients with inherited FVII deficiency (International Registry of Factor VII deficiency, IRF7; Seven Treatment Evaluation Registry, STER) was performed. RESULTS: In our cohort (N = 449; 215 male, 234 female), the higher prevalence of mucocutaneous bleeds in females strongly predicted ensuing gynaecological bleeding (hazard ratio = 12.8, 95% CI 1.68-97.6, P = 0.014). Menorrhagia was the most prevalent type of bleeding (46.4% of patients), and was the presentation symptom in 12% of cases. Replacement therapies administered were also analysed. For surgical procedures (n = 50), a receiver operator characteristic analysis showed that the minimal first dose of rFVIIa to avoid postsurgical bleeding during the first 24 hours was 22 µg kg(-1) , and no less than two administrations. Prophylaxis was reported in 25 women with excellent or effective outcomes when performed with a total weekly rFVIIa dose of 90 µg kg(-1) (divided as three doses). CONCLUSION: Women with FVII deficiency have a bleeding disorder mainly characterized by mucocutaneous bleeds, which predicts an increased risk of ensuing gynaecological bleeding. Systematic replacement therapy or long-term prophylaxis with rFVIIa may reduce the impact of menorrhagia on the reproductive system, iron loss and may avoid unnecessary hysterectomies.


Assuntos
Coagulantes/uso terapêutico , Deficiência do Fator VII/tratamento farmacológico , Fator VIIa/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifibrinolíticos/uso terapêutico , Criança , Pré-Escolar , Estudos de Coortes , Fator VII/análise , Feminino , Hemorragia/epidemiologia , Hemorragia/prevenção & controle , Humanos , Lactente , Masculino , Menorragia/epidemiologia , Pessoa de Meia-Idade , Fenótipo , Modelos de Riscos Proporcionais , Curva ROC , Proteínas Recombinantes/uso terapêutico , Sistema de Registros , Resultado do Tratamento , Adulto Jovem
14.
Andrologia ; 48(8): 860-79, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27681644

RESUMO

Infertility is defined as inability of a sexually active couple to conceive after 1 year of regular intercourse without contraception. Male factors account for 20%-50% of cases of infertility. The aim of this study was to review medicinal plants that proposed to improve sperm abnormalities in traditional Persian medicine. For this purpose, PubMed, Scopus, GoogleScholar and Cochrane library were explored for medicinal plants used in traditional Persian medicine for sperm abnormalities to obtain studies giving any evidence for their efficacy and pharmacological mechanisms related to male infertility. Data were collected for the years 1966 to March 2015. For some of them, including Chlorophytum borivilianum, Crocus sativus, Nigella sativa, Sesamum indicum, Tribulus terrestris, Mucuna pruriens and Withania somnifera, more reliable evidence was found. The mechanisms involved in the beneficial effects of medicinal plants in sperm abnormalities are antioxidant, anti-inflammatory, anti-oedematous and venotonic activity as well as containing precursors for sperm production and increasing blood testosterone level. Various phytochemical categories including saponins, phytosterols, carotenoids, oxygenated volatile compounds, phenolic compounds and alkaloids seem to be responsible for these beneficial effects. Further studies are recommended for obtaining more conclusive results about the efficacy and safety of the mentioned medicinal plants.


Assuntos
Astenozoospermia/tratamento farmacológico , Medicina Tradicional , Oligospermia/tratamento farmacológico , Fitoterapia , Preparações de Plantas/uso terapêutico , Alcaloides , Antioxidantes , Carotenoides , Clorófitas , Crocus , Medicina Baseada em Evidências , Humanos , Infertilidade Masculina/tratamento farmacológico , Irã (Geográfico) , Masculino , Nigella sativa , Fenóis , Fitosteróis , Preparações de Plantas/química , Plantas Medicinais , Saponinas , Sesamum , Tribulus
15.
Transfus Med ; 25(1): 8-12, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25801075

RESUMO

BACKGROUND: The problem of iron-overload observed in thalassemia patients can be overcome using chelating agents such as deferiprone (Ferroprox(®) ), deferasirox (Exjade(®) ) and deferoxamine (Desferal(®) ). Although these drugs can be used as monotherapy, combined therapy, especially deferiprone with deferoxamine, has led to promising outcomes in various studies. METHODS AND MATERIALS: In this quasi-experimental study, serum ferritin levels were evaluated in 32 ß-thalassemia major patients with severe iron overload before and after receiving combined deferasirox (30-40 mg kg(-1) day(-1) ) and deferoxamine (40-50 mg kg(-1) day(-1) ) 2 days a week. This study was conducted from September 2012 to September 2013 in Southern Iran. RESULTS: The mean of serum ferritin levels significantly reduced from 4031 ± 1955 to 2416 ± 1653 ng mL(-1) after 12 months of therapy (P < 0·001). Echocardiograph findings showed significant improvement 1year after end of the study (P < 0·001). No drug toxicity was observed by monitoring serum creatinine, liver enzymes and blood urea nitrogen (BUN) during the study period. We observed no correlation between mean serum ferritin change and age (P = 0·87). In addition, the mean serum ferritin change did not differ between male and female thalassemia patients (P = 0·454). No difference in mean serum ferritin change was observed between patients who had undergone splenectomy compared to those who had not done so (P = 0·307). CONCLUSION: The study suggests that combination chelating therapy with deferasirox and deferoxamine can effectively reduce iron burden in ß-thalassemia major patients with heavy iron overload without any significant complications.


Assuntos
Benzoatos/administração & dosagem , Desferroxamina/administração & dosagem , Sideróforos/administração & dosagem , Triazóis/administração & dosagem , Talassemia beta/tratamento farmacológico , Adolescente , Adulto , Criança , Deferasirox , Países em Desenvolvimento , Quimioterapia Combinada , Feminino , Ferritinas/sangue , Humanos , Irã (Geográfico) , Líbano , Masculino , Talassemia beta/sangue
16.
J Dairy Sci ; 98(10): 6865-75, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26233442

RESUMO

The objective of this study was to evaluate cooling to lessen the effects of heat stress during the last 3 wk of gestation on performance and behavior of multiparous Holstein cows. Twenty nonlactating cows were randomly assigned to treatments approximately 21 d before their expected calving date based on mature equivalent milk production and parity. Treatments were only imposed during the last 3 wk of gestation and included heat stress (HT; n=10) and cooling (CL; n=10), both under a similar photoperiod (14 h of light and 10 h of dark). Dry cows were housed in a sand-bedded stall with the stall areas for CL cows equipped with sprinklers and fans that were on from 0700 to 1900 h, whereas those for the HT cows were not. After parturition, all cows were housed in a barn with cooling devices. Rectal temperatures were measured daily at 1400 h and respiration rates were recorded by counting the flank movements for 1 min at 1500 h on odd days over the last 3 wk of gestation to calving. Daily dry matter intake was measured from -21 d relative to expected calving to 21 d after calving and milk production was recorded daily up to 180 d in milk. Behavioral changes of dry cows were studied continuously for 24 h at -10 d relative to expected calving. The average temperature-humidity index during the last 3 wk of gestation was 69.7 and was not significantly different between treatments. Heat-stressed cows exhibited greater rectal temperatures (39.5 vs. 39.2°C), greater respiration rates (70.4 vs. 63.3 breaths/min), and decreased dry matter intake (13.7 vs. 15.5 kg/d) compared with CL cows. Compared with HT cows, CL cows produced more milk during 180 d in milk (40.5 vs. 44.6 kg/d). Heat stress decreased ruminating (243.2 vs. 282.5 min/d) and chewing times (390.6 vs. 448.7 min/d) at -10 d before calving. The CL cows had shorter standing times than their HT counterparts (390.4 vs. 474.0 min/d). These results confirm that heat stress abatement in the late gestation period improves performance of dairy cows in subsequent lactation.


Assuntos
Comportamento Animal , Bovinos/fisiologia , Transtornos de Estresse por Calor/veterinária , Leite/metabolismo , Complicações na Gravidez/veterinária , Animais , Comportamento Animal/fisiologia , Doenças dos Bovinos , Ingestão de Alimentos , Feminino , Transtornos de Estresse por Calor/fisiopatologia , Temperatura Alta , Umidade , Lactação , Fotoperíodo , Gravidez , Complicações na Gravidez/fisiopatologia , Distribuição Aleatória , Taxa Respiratória
17.
Clin Exp Immunol ; 176(2): 180-9, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24387596

RESUMO

Down-regulation of soluble or membrane-bound co-stimulatory molecules by RNAi in dendritic cells can prevent the activation of immune responses. Therefore, this study was designed to evaluate the therapeutic efficacy of bone marrow-derived DCs (BMDCs) transduced with lentiviral vectors to permanently expressed shRNA specific for CD40 (CD40LV-DCs) and/or p19 subunit of interleukin (IL)-23 (p19LV-DCs) mRNAs in experimental autoimmune encephalomyelitis (EAE). In-vitro studies showed that double-transduced BMDCs (CD40(+) p19LV-DCs) resemble tolerogenic DCs due to profound down-regulation of CD40, lower expression of proinflammatory cytokines (IL-6 and IL-12), increased IL-10 production and stronger stimulation of myelin oligodendrocyte glycoprotein (MOG)35-55 -specific T cells for production of IL-10 compared with CD40LV-DCs, p19LV-DCs and BMDCs transduced with control lentiviral vector (CoLV-DCs). Moreover, injection of transduced CD40(+) p19LV- BMDCs in EAE mice resulted in more reduction in clinical score, significant reduction in IL-17 or increased production of IL-10 by mononuclear cells derived from the lymph nodes or spinal cord compared with CoLV-DCs-treated EAE mice. In conclusion, simultaneous knock-down of CD40 and IL-23 production by BMDCs may represent a promising therapeutic tool for the treatment of IL-17-dependent autoimmune diseases, including multiple sclerosis.


Assuntos
Antígenos CD40/imunologia , Células Dendríticas/imunologia , Encefalomielite Autoimune Experimental/imunologia , Subunidade p19 da Interleucina-23/imunologia , Células Th17/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Antígenos CD40/genética , Antígenos CD40/metabolismo , Proliferação de Células , Técnicas de Cocultura , Citocinas/imunologia , Citocinas/metabolismo , Células Dendríticas/metabolismo , Células Dendríticas/transplante , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/metabolismo , Encefalomielite Autoimune Experimental/terapia , Citometria de Fluxo , Humanos , Interleucina-10/imunologia , Interleucina-10/metabolismo , Interleucina-17/imunologia , Interleucina-17/metabolismo , Subunidade p19 da Interleucina-23/genética , Subunidade p19 da Interleucina-23/metabolismo , Lentivirus/genética , Camundongos , Camundongos Endogâmicos C57BL , Esclerose Múltipla/imunologia , Esclerose Múltipla/metabolismo , Esclerose Múltipla/terapia , Glicoproteína Mielina-Oligodendrócito/imunologia , Fragmentos de Peptídeos/imunologia , Interferência de RNA/imunologia , RNA Interferente Pequeno/genética , Células Th17/metabolismo , Resultado do Tratamento
18.
Haemophilia ; 20(6): 733-40, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25039531

RESUMO

Factor XIII congenital deficiency (FXIII CD) is a serious bleeding disorder resulting in a lifelong bleeding tendency, defective wound healing and recurrent miscarriage. The aim of this study was to review available literature on the burden and management of FXIII CD. To this end, Medline, Embase and Cochrane databases were searched. In current literature, FXIII CD is described as one of the most severe forms of a congenital coagulation disorder, primarily due to a high risk of severe bleeding events. The published literature suggests that over 50% of untreated FXIII CD patients experience severe bleeding symptoms. Intracranial haemorrhage (ICH)--a major cause of death and morbidity--is reported to occur in up to one-third of patients. Nonetheless, data on the social and financial burden in patients with FXIII CD are sparse. Identified reports on the effectiveness and safety of recommended treatments support that patients with FXIII CD should receive prophylactic treatment as early as possible in their lives to prevent the occurrence of bleeds, including potentially life-threatening ICHs. In conclusion, limited data on the social and economic consequences related specifically to FXIII CD have been published to date. However, it is widely acknowledged that the high risk of severe bleeds and ICH results in a high level of burden in patients with bleeding disorders. To inform future clinical decision-making and reimbursement decisions, further research is required to gain insight in how specifically FXIII CD affects quality of life and to fully understand associated economic consequences.


Assuntos
Efeitos Psicossociais da Doença , Deficiência do Fator XIII/diagnóstico , Deficiência do Fator XIII/terapia , Gerenciamento Clínico , Deficiência do Fator XIII/epidemiologia , Custos de Cuidados de Saúde , Humanos , Qualidade de Vida , Sistema de Registros , Inquéritos e Questionários
19.
East Mediterr Health J ; 20(11): 726-31, 2014 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-25601811

RESUMO

This study investigated the prevalence of iron-deficiency anaemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency and ß-thalassaemia trait among Arab migrating nomad children in southern Islamic Republic of Iran. Blood samples were analysed from 134 schoolchildren aged < 18 years (51 males, 83 females). Low serum ferritin (< 12 ng/dL) was present in 17.9% of children (21.7% in females and 11.8% in males). Low haemoglobin (Hb) correlated significantly with a low serum ferritin. Only 1 child had G6PD deficiency. A total of 9.7% of children had HbA2 ≥ 3.5 g/dL, indicating ß-thalassaemia trait (10.8% in females and 7.8% in males). Mean serum iron, serum ferritin and total iron binding capacity were similar in males and females. Serum ferritin index was as accurate as Hb index in the diagnosis of iron-deficiency anaemia. A high prevalence of ß-thalassaemia trait was the major potential risk factor in this population.


Assuntos
Anemia Ferropriva/etnologia , Deficiência de Glucosefosfato Desidrogenase/etnologia , Migrantes/estatística & dados numéricos , Talassemia beta/etnologia , Adolescente , Anemia Ferropriva/sangue , Anemia Ferropriva/etiologia , Anorexia/complicações , Árabes/estatística & dados numéricos , Criança , Estudos Transversais , Feminino , Ferritinas/sangue , Predisposição Genética para Doença , Deficiência de Glucosefosfato Desidrogenase/sangue , Deficiência de Glucosefosfato Desidrogenase/etiologia , Hemoglobina A2/análise , Humanos , Irã (Geográfico)/epidemiologia , Ferro/sangue , Masculino , Pica/complicações , Prevalência , Fatores de Risco , Abastecimento de Água/normas , Talassemia beta/sangue , Talassemia beta/etiologia
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